This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Movement disorders are a common source of disability. Among the most frequently diagnosed group of movement disorders is dystonia, defined by Fahn as "an abnormal movement characterized by sustained muscle contractions frequently causing twisting and repetitive movements or abnormal postures." Although dystonia may affect any part of the body, cervical dystonia, also called spasmodic torticollis, is the most common form in adults. Other examples include blepharospasm and focal action dystonia, so called writer's cramp. The first phase of the current study is focused on dystonic movement disorders. Although dystonia is sometimes induced by medications (tardive dystonia) or caused by other, underlying neurological disease the etiology of the majority of cases remains unknown. Some rare cases are genetically transmitted in an autosomal dominant pattern, and an abnormal gene, DYT1, has been identified in these families. However, most adults with dystonia have no family history of this disorder and do not carry the DYT1 gene. Little is known about other possible genetic contributions to these idiopathic cases. The paucity of scientific information on the pathogenesis of dystonia, including other genetic influences, has hampered the development of therapies. Recent clues regarding the possible pathogenesis of dystonia comes from convergence of two separate sources. The first1 suggests that abnormally increased cortical plasticity occurs among people with idiopathic cervical dystonia and also in people with dystonia who carry the DYT1 gene. People who are carriers of the DYT1 gene but do not have symptoms of dystonia were not found to have abnormally increased cortical plasticity. A second, possible clue, from Dr. Cramer's lab at UCI, is that cortical plasticity varies strongly in relation to a different gene. One's genotype for the protein Brain Derived Neurotrophic Factor (BDNF) strongly influences extent of cortical plasticity. Healthy subjects who have a val66met mutation in one or both alleles for the gene encoding BDNF have reduced measures of short-term cortical plasticity2. This genetic variation appears to have a powerful effect on many aspects of human brain function. For example, one study 3 noted that "Remarkably, the interaction between the BDNF val66met genotype and the hippocampal response during encoding accounted for 25% of the total variation in recognition memory performance." Together, these two observations suggest the hypothesis that persons who demonstrate dystonic symptoms, as compared to healthy subjects who do not have such symptoms, have overactive cortical plasticity, and thus a relatively lower incidence of the BDNF val66met genotype variant. The specific aim of the current study is to compare the frequency of the BDNF val66met genotype in persons diagnosed with dystonia to the frequency in healthy, non-dystonic controls. As a secondary aim, both subject groups will also be tested for the presence of the mutation in the DYT1 gene. The subhypothesis is that among the rare dystonic subjects who have the DYT1 gene mutation the absence of the val66met mutation in one or both alleles will be associated with an earlier age of onset and more severe level of dystonic symptoms, as compared to dystonic patients who carry this mutation. Note that one control group will be age-matched, healthy subjects. A second control group will be subjects with Parkinson's disease, also a basal ganglia disorder, but, unlike dystonia, due to neurodgeneration and with a pathophysiology presumed different than idiopathic dystonia.